From vores@hotmail.com Mon May 12 06:42:37 1997 Received: from f30.hotmail.com for vores@hotmail.com by www.ccl.net (8.8.3/950822.1) id GAA17483; Mon, 12 May 1997 06:31:13 -0400 (EDT) Received: (from root@localhost) by f30.hotmail.com (8.7.5/8.7.3) id DAA09142; Mon, 12 May 1997 03:30:41 -0700 (PDT) Message-Id: <199705121030.DAA09142@f30.hotmail.com> Received: from 158.250.32.157 by www.hotmail.com with HTTP; Mon, 12 May 1997 03:30:40 PDT X-Originating-IP: [158.250.32.157] From: "Alexey Serov" To: chemistry@www.ccl.net Subject: HyperChem ZINDO/1 file Content-Type: text/plain Date: Mon, 12 May 1997 03:30:40 PDT Hi! Can anybody write me what's principle of ZINDO/1 files. I want to insert some parameters in these files ( for elements after Xe ), but I don't know how to do it. Thanks. Alex. e-mail: vores@hotmail.com --------------------------------------------------------- Get Your *Web-Based* Free Email at http://www.hotmail.com --------------------------------------------------------- From maiden@RedBrick.DCU.IE Mon May 12 07:01:42 1997 Received: from tolka.dcu.ie for maiden@RedBrick.DCU.IE by www.ccl.net (8.8.3/950822.1) id GAA17334; Mon, 12 May 1997 06:07:39 -0400 (EDT) Received: from Nurse.RedBrick.DCU.IE by tolka.dcu.ie; (5.65v3.2/1.1.8.2/14Feb96-0535PM) id AA10631; Mon, 12 May 1997 11:05:25 +0100 Received: from localhost (maiden@localhost) by RedBrick.DCU.IE (SomeMTA) with SMTP id LAA15087 for ; Mon, 12 May 1997 11:06:48 +0100 (BST) Organisation: DCU Networking Society X-Disclaimer: The DCUNS is not responsible for the content of this message X-Award: Most Improved Society 1996-7 Date: Mon, 12 May 1997 11:06:48 +0100 (BST) From: "Michael Nolan LC4 (Wannabe Quantum Chemist)" To: Computational Chemistry List Subject: mn and cr complexes (Summary: part 2) Message-Id: Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII I'm trying this again, as it ended up in the rejected section, with all of the summary missing. That may have been due to its length. **************************************************************************** hi CCL!! here are the other excellent replies i recieved. answer 1: >From kless@chem.ucla.edu Thu May 1 08:13:28 1997 Date: Wed, 30 Apr 1997 11:29:34 -0700 (PDT) From: Achim Kless To: michael nolan Subject: Re: CCL:mn complexes Dear Michael, > I have a really bad problem and I cannot do anything about it. > Here it is: > I am trying to run ab-initio calculations on Mn(CO)3 and Cr(CO)3, using > GAMESS-UK. > I have tried the following methods (I also give if ti was succesful or > not): > > 1) RHF/3-21G (3-21G on all atoms) > for Mn(CO)3 this is successful, for Cr(CO)3 I get excessive number of > iterations and an oscillation of the energy. > > 3) RHF with minimal basis ECP on all atoms for Mn(CO)3 and Cr(CO)3. > This gives a ludicrously low energy (about -70a.u.), oscillations in the > energy and excessive number of iterations > > 5) RHF, min. basis ECP and ECPDZ on Mn, 3-21G and 6-31G on C and O try out the basis sets from A. Schaefer, C. Huber, and R. Ahlrichs. They are suitable especially for the middle-transition metals. See: Fully Optimized Contracted Gaussian Basis Sets of Triple Zeta Valence Quality for Atoms Li to Kr. A. Schaefer, C. Huber, and R. Ahlrichs; J. Chem. Phys. 100, 5829 (1994). Regarding ECPs check out the Pseudopotentials from M. Dolg, H. Stoll, H. Preuss. (http://www.theochem.uni-stuttgart.de) best regards, Achim --------------------------- Dr. Achim Kless UCLA, Dept. Chemistry and Biochemistry This was very helpful, I found these bais sets useful and also Dunning's double-zeta basis sets. ******************************************************************************* answer 2: >From her10531@argon.chem.tu-berlin.de Thu May 1 08:13:36 1997 Date: Wed, 30 Apr 1997 19:51:16 +0200 From: Rolad Hertwig To: michael nolan Subject: Re: CCL:mn complexes Micheal, welcome to the world of transition metal quantum chemistry! I will try to give you some hints, but in addition you should get in touch with people ( I mean personally), who have experience in the field, if your thesis advisor has not. > 1) RHF/3-21G (3-21G on all atoms) > for Mn(CO)3 this is successful, for Cr(CO)3 I get excessive number of > iterations and an oscillation of the energy. Oscillation is not unusual in organo-metallic complexes. Play around with SCF accelerators, like damping, diis, and shifting of virtual orbitals. There is no general recipe to avoid this. Also, change your starting geometry. Avoid too small bond lengths. Exploit symmetry, and specify electronic occupations explicitly as far as this is possible (I have little experience with GAMESS). > 3) RHF with minimal basis ECP on all atoms for Mn(CO)3 and Cr(CO)3. > This gives a ludicrously low energy (about -70a.u.), oscillations in the > energy and excessive number of iterations ECPs emulate the shielding of core electrons. Since these electrons are not treated explicitly, they do not contribute to the total energy, therefore you get small total energies. Do not compare total energies calculated with ECPs with those resuting from all electron calcs. > Does anyone have any ideas for how I can use ECPs (we are limited to about > 1.2GB) or anything else to get these calculations to run (we do not yet > have DFT). Okay, ECPs are not t h e solution to your problems as long as you do not have to worry about relativistic effects (Not crucial for 3d TMs). If you use them, be sure to use the basis set that comes along with them, since it has been specifically designed for that certain ECP. You do not necessarily need more than 1 GB of disk space, unless you are going to use correlated post-HF methods. DFT would be suitable for your case, since HF is rather inappropriate. However it is not te worst to start with. I hope I could give you some general clues, but it is not easy to do this via email for the problems you have. I would really recommend, you rip some money out of yor advisor's pockets and travel somewhere for a couple of weaks to learn the trade. Good luck! Roland ----------------------------------------------------------------------- Roland H. Hertwig Institut fuer Organische Chemie, TU-Berlin ******************************************************************************** answer 3: >From Philippe.Maitre@cth.u-psud.fr Thu May 1 08:13:45 1997 Date: Wed, 30 Apr 1997 18:55:26 +0200 From: Philippe Maitre To: Maiden@RedBrick.DCU.IE Subject: your Mn and Cr complexes, Dear Michael, I have had similar problems and I guess I could help you. You said "I assume the fact that Mn(CO)3 is positively charged has nothing to do with it (it is a closed shell)". I do not agree. The typical problem of SCF convergence with Transition Metal is that you have a near generacy of several d orbitals for low-coordination complexes. This leads to a near degeneracy of electronic configurations, which therby leads to a near degeneracy of determinants. And that's your problem in your iteration. This problem can be further complicated, sometimes, by pseudo potential. I do not have any experience with Gamess-UK, but with a Gaussian92 or Gaussian94, the internal guess of orbitals (either generated by diagonalizing HCORE or by using the extended Huckel approach) is extremely bad when using Pseudo-potential. Do not ask me why, I do not know. Just one more thing : this bad initial guess obtained when using a pseudo potential does not mean at all that the pseudo potentials are bad. There is a simple trick to converge an scf calculation with low-coordinationtransition metal system. You take a piece of paper and you find out the orbital energy level. For ML3 systems, you can look at "Orbital interaction in chemistry" by Albright, Burdett and Whangbo. Then, you find out a spin state (with the same numebr of electrons or not) which leads to a large energy difference between the Ground state electronic configuration and the first electronic one (i.e. where there is a large gap between the HOMO and the LUMO). Run an ROHF or RHF if this is a closed shell on this guy. This will converge easily. One it's done, reuse the converged orbitals of this calculation to calculate your system of interest. Good Luck, If you have any problem, do not hesitate to contact me. But please, give me a geometry and a spin state. Philippe Maitre Laboratoire de chimie theorique Batiment 490 Universite de Paris XI 91405 Orsay , FRANCE ************************************************************************* answer 4: >From tcundari@msuvx2.memphis.edu Thu May 1 08:13:52 1997 Date: Wed, 30 Apr 1997 11:57:30 -0600 From: Tom Cundari To: michael nolan Subject: Re: CCL:mn complexes Dear Michael, Noticed you said something about an RHF calc. What is the multiplicity of Cr(CO)3 and Mn(CO)3 fragments you are trying to converge on? Are you using symmetry? Another trick you can try with ECPs is to do a quick first calc on the 2nd row analogue (Mo for Cr, Tc for Mn) and if this converges use this wavefunction to start off a subsequent calculation of the first row metal. 2nd row transition metals often behave better in the SCF since their bonding is more covalent and hence the ligand fields are typically larger. At any rate, with ECPs the number of electrons should be the same and the symmetry props of the MOs should be similar. Good luck. Tom Tom Cundari Associate Professor Department of Chemistry University of Memphis (under T in the ACS Grad Directory!) ***************************************************************************** answer 5: From: chemistry-request (SMTPMAIL.chemistr) at PROFGATE Date: 4/30/97 9:57AM To: Michelle Pietsch at BVL60PO *To: C=us; A= ; P=Internet; DD.RFC-822=chemistry(a)www.ccl.net at X.400 Subject: CCL:mn complexes ------------------------------------------------------------------------------- Michael, To force convergence, increase the value of LEVEL (keyword for GAMESS-UK). You may increase this value until you force convergence. Once the wave function is converging, decrease the value for LEVEL little by little until it is at its default value. Using a large value for LEVEL will force convergence but it may converge in the wrong state. After convergence, print out your molecular orbitals and make sure that the correct orbitals are occupied. If the correct orbitals are not occupied, use the SWAP command to exchange occupied and virtuals until the correct orbitals are occupied. Always check to make sure that you have the correct orbitals occupied after using the SWAP command. You may want to examine the molecular orbitals before convergence and make any SWAPs at that time. I have found this procedure to work well for systems containing Cr and other metals. You should be able to use ECPs and any basis set. However, increasing the number of valence functions will increase the difficulty of convergence. Best of Luck, Mickey ******************************************************************************* answer 6: >From bianco@lord.Colorado.EDU Thu May 1 08:14:04 1997 Date: Wed, 30 Apr 1997 09:13:44 -0600 (MDT) From: Roberto Bianco To: michael nolan Subject: Re: CCL:mn complexes Hi Michael, looking at the Metal-C distance of 1.8 angstrom you give below, my guess is that the atomic centers are too far apart for the wavefunction to converge. I would try with initial, artificially shorter Metal-C distances (say 1.2-1.4 A) to achieve convergence, and then let the geometry relax (optimize) through small steps, such that the "memory" of the converged wavefunction is not lost in the process. Roberto -- Roberto Bianco / Department of Chemistry & Biochemistry University of Colorado / Campus Box 215 / Boulder, CO 80309 / USA bianco@lord.colorado.edu / phone +(303) 492-3504 / fax +(303) 492-5894 ************************************************************************** answer 7: >From E.A.Moore@open.ac.uk Fri May 9 09:55:50 1997 Date: 1 May 1997 10:08:10 +0100 From: "E.A.Moore (Elaine Moore)" To: michael nolan Subject: Mn and Co complexes Transition metal complexes are vey tricky. You can try 1) Altering the guess option 2) Putting damping on to converge and then feeding the resulting orbitals back in with the damping off 3) reordering the orbitals ECP energies will be smaller because of the missing core electrons. Elaine A. Moore e.a.moore@open.ac.uk ***************************************************************************** Michael Der Kobold hat gesprochen ****************************************************************************** Michael Nolan (nearly BSc.) Dublin City University (quantum chem.) 41 Woodview Chemistry + German Year 4 Lucan Co. Dublin Ireland / Republic of Ireland / ROI / Eire Email: Maiden@redbrick.dcu.ie ****************************************************************************** From akutatel@du.edu Mon May 12 11:56:27 1997 Received: from odin.cair.du.edu for akutatel@du.edu by www.ccl.net (8.8.3/950822.1) id LAA20544; Mon, 12 May 1997 11:04:02 -0400 (EDT) Received: by odin.cair.du.edu; id AA31994; Mon, 12 May 1997 09:03:41 -0600 Received: by kizh.biochem.du.edu with Microsoft Mail id <01BC5EB2.DD712260@kizh.biochem.du.edu>; Mon, 12 May 1997 08:59:57 -0600 Message-Id: <01BC5EB2.DD712260@kizh.biochem.du.edu> From: Andrei Kutateladze To: "'CCL'" Cc: "'toukie@zui.unizh.ch'" Subject: CCL: SUMMARY: Torsional barriers for methyl group rotation Date: Mon, 12 May 1997 08:59:56 -0600 Mime-Version: 1.0 Content-Type: text/plain; charset="us-ascii" Content-Transfer-Encoding: 7bit I apologize in advance if this message reaches you twice: A week ago I posted the following question: > A colleague of my is looking for reliable experimental data on >torsional barriers for methyl group rotation in various environments - >aromatic, n-alkyl, branched alkyl, ether etc. > Any references will be much appreciated. Many thanks to people who replied. Special thanks to Wolfgang Roth for quite a comprehensive refs list. Andrei Kutateladze University of Denver SUMMARY: =========================================== REPLY # 1 You may look at this http://www-public.rz.uni-duessledorf.de/~rothw/diplom/literatur.html part of my homepage where I placed the list of literature from my dissertation. Experimental methyl group torsion parameters of aromatic compounds are available fo the following molecules (to my knowledge): toluene (see Refs. 15, 29, 56 of the above mentioned website, see also J. Chem. Phys. 102 (1995) 6787, J. Chem. Phys. 102 (1995) 8718) 1-methyltetrazene (Refs. 44, 58) 3-fluortoluene (Ref. 27) 4-fluortoluene (Refs. 27, 44) (I wasn't interested in 2-fluortoluene) cis-3-cresol (Ref. 13) 3-methylindole (Ref. 59) 5-methylindole (Refs. 41, 59) 6-methylindole (Ref. 41) 3- and 4-methylbenzylradical (Ref. 28) 2-Methylpyrazine (Ref. 60) 2-Methylnaphthalene (Ref. 17) (data for 1-MN are also available) methylcyclopentadienylradical (Ref. 20) 4- and 5-methylpyrimidine (Ref. 38) 4-toluidine (Refs. 42, 54) Further molecules which have been investigated are xylenes acetone (lot of papers in J. Molec. Spect., maily from IR spectra for different torsional modes. methylglyoxale (Ref. 73) methanol (very early microwave papers in J. Chem. Phys.) CH3SH trans-beta-methylstyrene (J. Phys. Chem. 99 (1995) 4386 acetaldehyde (e.g. J. Mol. Struct. 350 (1995) 83) methyl-subtituted stilbenes (work of Spangler and coworkers, e.g. J. Phys. Chem. 99 (1995) 9316) methylacetylene ... I decided to cut the list here because I have approximately 100 to 150 references to experimental and theoretical papers dealing with internal rotation maily of the methyl group. I don't have informations about ether because this molecules are not accessible to medium or high resolution laser induced fluorescence. If You/Your colleague is interested in the whole list which is an Excel 4.0 file, please send me an email. Regards Wolfgang Roth ====================== REPLY # 2 Andrei, The following reference might be useful: Cohen, N.; Benson, S. W. In "The chemistry of Alkanes and Cycloalkanes"; Patai, S.; Rappoport, Z., Ed.; John Wiley, 1992; Chapter 6. Regards, Ashutosh (Misra Ashutosh, ashutosh@jove.acs.unt.edu) ======================= REPLY # 3 Dear Andrei Kutateladze, There is a table of about twenty or so methyl barriers in a book on thermodynamics: "Thermodynamics of Organic Compounds in the Gas State", Volume I, Michael Frenkel, K.N. Marsh, R. C. Wilhoit, G. J. Kabo, G. N. Roganov page 26. A recent paper in JCP deals with internal rotation treated by ab innitio methods, and some of references there may lead to experimental data. Russ Dr. Russell D. Johnson III Research Chemist Physical and Chemical Properties Division National Institute of Standards and Technology Gaithersburg, MD 20899 email: russell.johnson@nist.gov From Y0H8797@ACS.TAMU.EDU Mon May 12 12:42:54 1997 Received: from VMS2.TAMU.EDU for Y0H8797@ACS.TAMU.EDU by www.ccl.net (8.8.3/950822.1) id LAA21114; Mon, 12 May 1997 11:53:59 -0400 (EDT) Date: Mon, 12 May 1997 10:53:28 -0500 (CDT) From: YONG HUANG To: CHEMISTRY@www.ccl.net Message-Id: <970512105328.204bb15d@ACS.TAMU.EDU> Subject: Re:CCL:another type of discussion in CC >From: SMTP%"hxt10@po.cwru.edu" 12-MAY-1997 09:48:41.67 >Subj: CCL:another type of discussion in CCL > >Dear CCLers: > > I have one suggestion about the type of discussions in CCL. >If we can post research results on CCL, then it may work like >the electric conference. Based on that, everyone can focus on >interesting research topics and can have deeper discussion. >I think we can exchange our research experience quickly by this way. >What do you think? Any comment? > >Hui-Hsu (Gavin) Tsai I totally agree. Although CCL is very helpful in terms of finding a specific software package, literature search etc., I'm much more interested in chemistry. In whatever way, your research results or your review of a book or article or simply a "brainstorm" idea, post it. I promise I won't delete a single message like this after reading the Subject line, as I do to a message titled "CCL:Any Program to do blahblahblah?". Excellent idea, Gavin. BTW, you mean electronic conference, not electric conference, don't you? Learn from my lessons. If you post a brainstorm idea, be careful or people will laugh at you. But I know CCL members are nice tolerant people. Yong From ccl@www.ccl.net Mon May 12 13:42:42 1997 Received: from bedrock.ccl.net for ccl@www.ccl.net by www.ccl.net (8.8.3/950822.1) id NAA21894; Mon, 12 May 1997 13:16:58 -0400 (EDT) Received: from wugate.wustl.edu for reichertd@mirlink.wustl.edu by bedrock.ccl.net (8.8.3/950822.1) id NAA09745; Mon, 12 May 1997 13:16:55 -0400 (EDT) Received: from mirlink.wustl.edu (mirlink.wustl.edu [128.252.155.1]) by wugate.wustl.edu (8.8.5/8.8.5) with SMTP id MAA19563 for ; Mon, 12 May 1997 12:16:55 -0500 (CDT) Message-ID: Date: 12 May 1997 12:14:23 -0500 From: "David Reichert" Subject: MD and continuum solvation To: "CCL post" X-Mailer: Mail*Link SMTP-MS 3.0.2 Dear Netters, I'm hoping that someone out there can provide me with some leads. I'm looking for some software that can do molecular dynamics in an aqueous solvation continuum. The only package I've found so far is MacroModel, are there any others out there? Thanks, ************************************************ * David E. Reichert, Ph.D. * * Mallinckrodt Inst. of Radiology * * Div. Radiological Sciences, * * Washington University School of Medicine * * 510 S. Kingshighway Blvd., Campus Box 8225 * * St. Louis, MO 63110 * * * * phone: (314)362-8461 * * fax: (314)362-9940 * * e-mail: reichertd@mirlink.wustl.edu * ************************************************ From Vladislav.Vassiliev@BRI.NRC.CA Mon May 12 18:42:45 1997 Received: from bravais.BRI.NRC.CA for Vladislav.Vassiliev@BRI.NRC.CA by www.ccl.net (8.8.3/950822.1) id RAA24965; Mon, 12 May 1997 17:58:33 -0400 (EDT) Received: from rio.BRI.NRC.CA by bravais.BRI.NRC.CA with ESMTP id RAA29365; Mon, 12 May 1997 17:59:49 -0400 Received: from localhost by rio.BRI.NRC.CA with SMTP id RAA25318; Mon, 12 May 1997 17:59:46 -0400 Date: Mon, 12 May 1997 17:59:46 -0400 (EDT) From: Vladislav Vassiliev X-Sender: vlad@rio.BRI.NRC.CA To: CHEMISTRY@www.ccl.net Subject: Summary: How to calculate pKa values in large proteins?... Message-ID: MIME-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII Dear CCL members, Recently, I sent out the following post: +++++++++++ BEGIN ORIGINAL MESSAGE ++++++++++++++ Let's imagine I have coordinates of a real protein (for example, from PDB) and now I would like to know the pKa values of all the residues (Asp's, Glu's, Lys's, Arg's, His's) at a given pH. What kind of programs could predict these pKa values? I would also be interested in any references concerning the approaches of this kind of prediction. ++++++++++++ END OF ORIGINAL MESSAGE ++++++++++++++++ Here is a summary of the responses. Many thanks to all who responded. ++++++++++++++++++++++++++++++++++++++++++++++++++++++ From: Paul Beroza Several research groups have investigated this problem, commonly referred to as the "multiple site titration problem". The most widespread approach is to assume that the pKa of a titrating residue is perturbed from its solution value by the electrostatic environment it experiences in the protein. The electrostatic energies involved can be calculated from continuum models using finite difference, and other, numerical methods. I've appended a list of references dealing with the subject (liberally sprinkled with references to my own work, of course). There are many more. I think the Bashford and Karplus paper is a good place to start, though more recent work uses more sophisticated models. Alternatively, Arieh Warshel has a more microscopic PDLD model (protein dipoles langevin dipoles) which has also been applied to pKa calculation in proteins. Several available computer programs can do these sorts of calculations: MEAD (from Don Bashford ftp.scripps.edu:pub/bashford) pep (my finite difference code ftp.scripps.edu:pub/beroza) DELPHI (from Barry Honig's group) UHBD (from Andy McCammon's group) polaris (from Arieh Warshel's group) --------------------------------------------------------------- @ARTICLE{Russel, AUTHOR="S. T. Russel and A. Warshel", JOURNAL="J. Mol. Biol.", TITLE="The Energetics of Ionized Groups in Bovine Pancreatic Trypsin Inhibitor", VOLUME="185", PAGES="389-404", YEAR="1985" } @ARTICLE{Bashford90, AUTHOR="D. Bashford and M. Karplus", JOURNAL="Biochemistry", TITLE=" {${\rm pK_a}$'s} of Ionizable Groups in Proteins: Atomic Detail from a Continuum Model", VOLUME="29", PAGES="10219-10225", YEAR="1990" } AUTHOR="P. Beroza and D. R. Fredkin and M. Y. Okamura and G. Feher", JOURNAL="Proc. Natl. Aca. Sci.", TITLE="Protonation of Interacting Residues in a Protein by a {M}onte {C}arlo Method: {A}pplication to Lysozyme and the Photosynthetic Reaction Center of {{\it Rhodobacter sphaeroides}}", VOLUME="88", PAGES="5804-5808", YEAR="1991" } @ARTICLE{Oberoi93, AUTHOR="H. Oberoi and N. M. Allewell", JOURNAL="Biophys. J.", TITLE="Multigrid Solution of the Nonlinear Poisson-Boltzmann Equation and Calculation of Titration Curves", VOLUME="65", PAGES="48-55", YEAR="1993" } @ARTICLE{Yang93, AUTHOR="A.-S. Yang and M. R. Gunner and R. Sampogna and K. Sharp and B. Honig", JOURNAL="Proteins", TITLE="On the Calculation of {${\rm pK_a}$'s} in Proteins", VOLUME="15", PAGES="252-265", YEAR="1993" } @ARTICLE{Antosiewicz94, AUTHOR="J. Antosiewicz and J.A. McCammon and M.K. Gilson", TITLE="Prediction of pH-dependent Properties of Proteins", JOURNAL="J. Mol. Biol.", VOLUME="238", PAGES="415-436", YEAR="1994" } @ARTICLE{You95, AUTHOR="T.J. You and D. Bashford", TITLE="Conformation and hydrogen ion titration of proteins: a continuum electrostatic model with conformational flexibility", JOURNAL="Biophys. J.", VOLUME="69", PAGES="1721-1733", YEAR="1995" } @ARTICLE{Beroza95, AUTHOR="P. Beroza and D. R. Fredkin and M. Y. Okamura and G. Feher", JOURNAL="Biophys. J.", TITLE="Electrostatic Calculations of Amino Acid Titration and Electron Transfer, {${\rm Q_A^- Q_B \rightarrow Q_A Q_B^-}$}, in the Reaction Center", VOLUME="68", PAGES="2233-2250", YEAR="1995" } @ARTICLE{Beroza96, AUTHOR= "P. Beroza and D. R. Fredkin", TITLE="Calculation of Amino Acid {${\rm pK_a}$s} in a Protein from a Continuum Electrostatic Model: Method and Sensitivity Analysis", JOURNAL="J. Comp. Chem.", VOLUME="17", PAGES="1229-1244", YEAR="1996" } @ARTICLE{Beroza96, AUTHOR= "P. Beroza and D. A. Case", TITLE="Including Side Chain Flexibility in Continuum Electrostatic Calculations of Protein Titration", JOURNAL="J. Phys. Chem.", VOLUME="100", PAGES="20156-20163", YEAR="1996" } +++++++++++++++++++++++++++++++++++++++++++++++++++++++++++ From: "Andrey Bliznyuk" Two recent references are: 1. J. Comp. Chem. 1996, v.17, N14, p.1633-1644 2. J. Phys. Chem. 1995, v.99, pp.7180-7187 see also a refs inside. Unfortunately, there is no reliable method to do the predictions. Even the best methods [ref.1] may routinely give an error of about 1 pK unit. The reason, I believe, is that current MM forcefield do not have a good charge model, i.e. charges are located at the atomic centers and are not polarizable. While it seems to be not very limiting while doing interaction energy calculations, the pKa calculations fails. I tried several FF (Amber, OPLS, Charm, Gromos, CFF91) and could not reproduce the pKa shift going from CH3COOH to C2H5COOH. Hence, I would not trust the enzyme pKa calculations. +++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++ From: Stefan Grzybek There are different approaches available for this kind of calculation. The main differences are how the electrostatic potentials and interaction energies are calculated and how the interacting charges are treated to calculate ionization states. To the first point: It is possible to calculate the electrostatic interactions simply using Coulomb's law with an appropriately choosen dielectric constant or to use solutions of the Poisson-Boltzmann equation to calculate interaction energies. The most programs I know of, use solutions to the Poisson-Boltzmann equation for calculating interaction energies. The second point: First is possible to use the Tanford-Roxby approximation to solve the problem of interactiong ionization states; however this breaks down if there are strongly interacting residues present. Better is to consider the real statistical mechanical average over all possible ionization states. This however has the drawback that calculating the ionization states of a small protein with only about 25 to 30 ionizable residues already becomes problematic. Therefore people have invented the 'reduced site' approximation, monte carlo methods or mixed tanford-roxby/statistical mechanics methods. Recent developments in this field focus on the incorporation of protein dynamics or sidechain flexibility into the treatment of pK-calculations. Some programs I know of: MacroDox by Scott H. Northrup (uses the Tanford-Roxby approximation) http://pirn.chem.tntech.edu/macrodox.html MEAD by Donald Bashford (bashford@scripps.edu) ftp://ftp.scripps.edu/pub/electrostatics/ There has also been developed a pk-calculation program suite in the lab of Barry Honig by Andreas Windemuth. Mail to pka@cumbnd.bioc.columbia.edu or windemut@cumbnd.bioc.columbia.edu for further information. Since there is a large amount of literature in this field, I don't append a list here. If you are interested, please contact me directly. ++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++ From: Mohamad Aman Jairajpuri I got your forwarded letter enquiring about the calculation of pKa of ionizable group in proteins through one of the profs in my department. I have been involoved in such type of pKa calculations for the last six months using finite difference poission boltzmann algorithim developed by Dr James Warwicker. These are a complex set of programms in FORTRAN and requires VMX/VAX environment for the operation. I have used this programm extensively for the calculation of pKa of arginines in several proteins. The programm is not commercialized and hence is in an extremely crude form and very very difficult to impliment. Fortunately I was able to use it after much effort and it finally paved the way for my thesis, (where I was able to match experimentally determined pKas with that of the theoritical) which I would be writing soon. This programm can be down loaded from FTP site (FTP calvados.ukc.ac.uk) If you need any help I would be willing to help you. You can also obtain a programm developed by Dr Gilson and Dr McCammon for the calculation of the pKa in proteins. This is a commercial programm which is routinely released to academic institution on very nominal costs ($400 approx). You can contact Dr J. Andrew McCammon at Department of Chemistry and Biochemistry, university of California at San Diego, La Jolla, California 92093-0365.